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Journal Article

Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment

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Cavalcanti-Adam,  Elisabetta Ada
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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http://www.cell.com/cancer-cell/pdf/S1535-6108(17)30016-8.pdf
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http://dx.doi.org/10.1016/j.ccell.2017.02.002
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Citation

Seckinger, A., Delgado, J. A., Moser, S., Moreno, L., Neuber, B., Grab, A., et al. (2017). Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell, 31(3), 396-410. doi:10.1016/j.ccell.2017.02.002.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002C-C266-9
Abstract
We identified B cell maturation antigen (BCMA) as a potential therapeutic target in 778 newly diagnosed and relapsed myeloma patients. We constructed an IgG-based BCMA-T cell bispecific antibody (EM801) and showed that it increased CD3+ T cell/myeloma cell crosslinking, followed by CD4+/CD8+ T cell activation, and secretion of interferon-γ, granzyme B, and perforin. This effect is CD4 and CD8 T cell mediated. EM801 induced, at nanomolar concentrations, myeloma cell death by autologous T cells in 34 of 43 bone marrow aspirates, including those from high-risk patients and patients after multiple lines of treatment, tumor regression in six of nine mice in a myeloma xenograft model, and depletion of BCMA+ cells in cynomolgus monkeys. Pharmacokinetics and pharmacodynamics indicate weekly intravenous/subcutaneous administration.